Mingyang Song1,2,3, Yan Zheng3, Lu Qi3,4,5, Frank B Hu3,4,6, Andrew T Chan1,2,4,7, Edward L Giovannucci3,4,6. 1. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 2. Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA. 3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 4. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 5. Department of Epidemiology, Tulane University, New Orleans, LA, USA. 6. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 7. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
Abstract
Background: The genetic associations with trajectories of body fatness over the life course remain unknown. Methods: We used a group-based modelling approach to identify trajectories of body fatness from age 5 years up to 65 for 7277 women from the Nurses' Health Study and 4645 men from the Health Professionals Follow-up Study. We created a genetic risk score (GRS) based on 97 variants associated with adulthood body mass index (BMI) and estimated its association with trajectories using logistic regression. Results: We identified four distinct trajectories: lean-medium, medium-medium, lean-heavy and medium-heavy. The GRS increased across the four groups in that order (P < 0.001); 47% of women and 45% of men in the first decile of the GRS were in the lean-medium group, and these proportions reduced to 26% and 28%, respectively, for the highest decile. The corresponding proportions in the medium-heavy group were 8% and 5%, increasing to 21% and 14%, respectively. For women, compared with the odds of being in the lean-medium group, a 10-allele increment in the GRS was associated with a 40% [95% confidence interval (CI), 27-54%], 43% (30-58%), and 115% (91-143%) increase in the odds of being in the medium-medium, lean-heavy and medium-heavy groups, respectively. For men, the corresponding increases in the odds were 26% (12-42%), 27% (13-43%), and 81% (53-115%), respectively. Conclusions: Individuals with genetic variants for adulthood BMI were more likely to maintain a heavy body shape and gain weight throughout life. These findings support a persistent effect of genetic variants on body fatness across the lifespan.
Background: The genetic associations with trajectories of body fatness over the life course remain unknown. Methods: We used a group-based modelling approach to identify trajectories of body fatness from age 5 years up to 65 for 7277 women from the Nurses' Health Study and 4645 men from the Health Professionals Follow-up Study. We created a genetic risk score (GRS) based on 97 variants associated with adulthood body mass index (BMI) and estimated its association with trajectories using logistic regression. Results: We identified four distinct trajectories: lean-medium, medium-medium, lean-heavy and medium-heavy. The GRS increased across the four groups in that order (P < 0.001); 47% of women and 45% of men in the first decile of the GRS were in the lean-medium group, and these proportions reduced to 26% and 28%, respectively, for the highest decile. The corresponding proportions in the medium-heavy group were 8% and 5%, increasing to 21% and 14%, respectively. For women, compared with the odds of being in the lean-medium group, a 10-allele increment in the GRS was associated with a 40% [95% confidence interval (CI), 27-54%], 43% (30-58%), and 115% (91-143%) increase in the odds of being in the medium-medium, lean-heavy and medium-heavy groups, respectively. For men, the corresponding increases in the odds were 26% (12-42%), 27% (13-43%), and 81% (53-115%), respectively. Conclusions: Individuals with genetic variants for adulthood BMI were more likely to maintain a heavy body shape and gain weight throughout life. These findings support a persistent effect of genetic variants on body fatness across the lifespan.
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